In most tropical areas where malaria is endemic, young children are most prone to develop severe malaria, and eventually to die. Despite a recent decrease in malaria mortality due to extensive malaria control through insecticide impregnated bednets and increased use of artemisinin derivatives, 275,000 African children still die every year from malaria. Cerebral malaria is the most severe form of malaria, a neuropathology that may lead to death or neurological sequelae. Pathophysiology of cerebral malaria is complex and multifactorial. Plasmodium falciparum-infected erythrocytes adhere to vascular endothelium and other erythrocytes in brain, cause microvascular obstruction, elicit a local inflammation, blood brain barrier impairment and a range of immune cellular host responses aiming to resolve this process of neuroinflammation. Thus, cerebral malaria cure depends on both parasite neutralization and brain inflammation resolution. The NEUROCM project will study both aspects. It is currently believed that cerebral malaria is caused by dedicated parasite variants that specifically localize in brain through interaction between parasite proteins expressed on the surface of infected red blood cells and brain endothelium. The NEUROCM project aims to identify these parasite proteins. To achieve this, parasite variants originating from two clinical groups of patients (uncomplicated and cerebral malaria) will be compared using a proteogenomic approach. Identified proteins will then be functionally characterized by a cellular and molecular biology approach. Parasite sequestration and interaction with brain endothelium lead to host immune response resulting in neuroinflammation. The mechanical obstruction of brain blood flow leads to hypoxia and local inflammatory state. This important dysregulation triggers two critical mechanisms: activation of microglia (the brain resident macrophages) and influx of myeloid immune cells to the brain. NEUROCM will focus on both mechanisms to identify molecular targets of the cellular host immune response to infection useful to promote the resolution of neuroinflammation. In order to reach this objective, our project will initially include experimental work before validation in humans. The human study will include the same two groups of malaria patients (uncomplicated and cerebral malaria), and an additional group of non-malarial coma. Our experimental murine models will allow the formulation of new scientific hypothesis while proof of concept will be achieved through the correlation of our proposed targets with patient morbidity and mortality parameters. In addition, the diagnosis of cerebral malaria is always difficult, and a coma in the presence of malaria parasites in the peripheral blood is often considered as cerebral malaria in endemic countries. NEUROCM will allow to differentiate the different etiologies by extensive blood biochemistry and molecular diagnosis in CSF of microbial infections. Thus, NEUROCM will provide, for the first time, an accurate differential diagnosis of cerebral malaria, as well as the identification of the causes of coma in the African child. The final products of NEUROCM are expected to feed the pipeline of new therapeutic (immune intervention) and preventive (vaccine) strategies that will improve cerebral malaria outcome, as well as other diseases involving neuroinflammation.

Traditional medicine is an intangible cultural heritage which is used by 10 to 60% of people depending on the country. Its role is predominant in the achievement of seven sustainable development goals and targets. In French Polynesia, Polynesians (called ma’ohi) is the main indigenous group and represent 60% of the total population. They are known to have extensive traditional medical knowledge (TMK) with about 150 medicinal plants reported, and with gastrointestinal ailments as one of the main disorders treated. However, their TMK is threatened by various socio-cultural (lack of knowledge transmission), ecological (extinction of some medicinal plants due to overuse and climate change) and sanitary factors (health safety concerns due to misuse). SUSTAINMEDPOL aims to contribute to the sustainability of TMK in French Polynesia by analyzing these factors, sources of global pressure, developing new strategies of sustainability, and proposing solutions (plant conservation strategies, training program, scientific validation for official integration into the local health system). Diarrheal illnesses, highly prevalent in this territory and associated with various disorders, will be used as an object of study. SUSTAINMEDPOL is built around four work packages (WP). WP1,2&3 are chronologically ordered and imbricated to develop and propose tangible solutions that will be implemented in the WP4. Overall, SUSTAINMEDPOL is an interdisciplinary project involving original and innovative tools (online and on-site survey, multiple stakeholders at local and regional scales, replacement of mammals in lab experiments) from the fields of botany, ecology, pharmacology, phytochemistry and sociology. The scientific coordinator of this project is one of the few specialists in ethnopharmacology (interdisciplinary study of TMK) in France, and has developed strong collaborations with local experts in conservation and sociology, as well as internationally recognized biologists and chemists.

This project aims to generate major breakthroughs in the quantification of ecosystem services provided by biodiversity in agro-ecosystems in the lower Mekong basin, a region facing dramatic environmental and societal changes. In this region, paddy fields appear as mosaics owing to the presence of mounds built by termites. While these structures seem comparable to hedgerows or bocage areas in temperate ecosystems, their impacts on the sustainability of agricultural systems and the livelihood of farmers remain unknown. Therefore, ECO-TERM project proposes to characterize and quantify the ecological (e.g., impact on animal and plant biodiversity), environmental (e.g., impact on soil and water dynamic, pesticide utilization, rice resistance and production) as well as socio-economical processes (e.g., impact on food security, human health, and farmer’s incomes) impacted by these patches of biodiversity and fertility in Cambodia, in adequacy with the axis 1.6 and the Sustainable Development Goals n°1, 2, 3, 8, 12, 13, 15 and 17. This project is built around 3 inter-connected scientific work packages (WPs) and on a WP dedicated to the coordination of cross-cutting activities and the co-construction of knowledge by making farmers and scientists interact within participatory workshops. This project brings together 5 French academic partners and self-funded research units in Cambodia, one local NGO, and one society specialized in the utilization of participatory modelling and role playing games. It requires the recruitment of a PhD student, with transversal activities between WP, and a postdoc for two years (only one year requested to ANR) for the construction of econometric models.

Modern society is subject to current environmental constraints due to the presence of pollutants in air, water or soil generating an alarming increase in allergic phenomena in the population. This chronic disease is steadily increasing since 40 years, leading from long-term human health deterioration to serious body reactions (anaphylaxis). Most of the allergens consist in (glyco)-proteins from various origins such as pollen, dust mites, and food products (both animals and plants). Commercial analogic diagnosis solutions exist such as skin test or biochip technology (ISAC test) but are not fully adapted to answer the community involvement. They mainly suffer from a lack of sensitivity or a prohibitive cost. Moreover, their methodology does not allow screening the complete human allergenic cartography. The DIALMIB project proposes a new digital approach for a multiplexed diagnosis of allergy, in conceptual break with the existing analog biochip technologies. DIALMIB is based on a microparticles color-code technology in liquid medium. This technology should allow the specific detection of IgE in patient’s sera with colored microbeads functionalized with allergen extracts from different sources. Coupling magnetic sorting, thermodynamic assembly and ultra-sensitive digital microbead lens-free analysis, this low-cost technology should increase the possibilities of the test (cross-allergies detection possibilities) and democratize it. This project aims at providing a commercial solution including a diagnosis tool and consumables (reaction kit). Industrial transfer of this technology would open the market of clinical diagnosis to a start-up company issued from two of the project’s academic partners. If succeed, this digital microbeads technology could address other health applications (oncology, neurodegenerative diseases…) involving protein detection